Taltz ® (ixekizumab) injection

80 mg/mL

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

How should TALTZ® (ixekizumab) be used in patients with hepatic impairment?

No formal trial of the effect of hepatic impairment on the pharmacokinetics of ixekizumab was conducted.

General Information

No formal trial of the effect of hepatic impairment on the PKs of ixekizumab was conducted. The prescribing information does not provide recommendations for dosage adjustment in patients with hepatic impairment.1

Study exclusion criteria for all clinical trials included having a hepatic disorder that, in the opinion of the investigator, poses an unacceptable risk to the patient if participating in the study or of interfering with the interpretation of data; or having AST or ALT levels more than 2.5 times ULN.2-6

Ixekizumab is a monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgGs.1

Hepatic Safety Clinical Trial Data

Brief descriptions of the pivotal clinical trials for moderate-to-severe PsO, active PsA, and active axSpA are provided at the end of this response. Detailed clinical trial descriptions are available upon request.

Note that data from multiple, different dosing regimens, including unapproved doses, are included in this response.

Psoriasis: Hepatic Safety From UNCOVER Clinical Trials

An integrated analysis of the phase 3 clinical trials demonstrated no significant differences between ixekizumab treatment groups and placebo, during either the 12-week induction or 48-week maintenance periods, in the proportions of patients with treatment-emergent elevations in

  • ALT or AST ≥3 times ULN, 5 times ULN, and 10 times ULN, or

  • alkaline phosphatase >2 times ULN.6

The percentages of patients reporting hepatic-related AEs were similar across the treatment groups in the induction and maintenance periods.6

Overall there were no clinically important changes from baseline in mean liver biochemical test results (ALT, AST, total bilirubin, alkaline phosphatase) in any treatment group in ixekizumab patients compared to placebo or etanercept patients in the 12-week induction period of the active-controlled pivotal trials UNCOVER-2 and UNCOVER-3.5 In the PsO population, longer-term exposure with ixekizumab is not associated with an increase in clinically important hepatic-related laboratory changes or with an increased risk of hepatic-related AEs.6

Psoriatic Arthritis: Hepatic Safety From SPIRIT Clinical Trials

Analyses of hepatic-related laboratory analytes and hepatic-related AEs do not demonstrate clinically important adverse effects related to ixekizumab treatment in patients with PsA. No patient in the PsA population met the laboratory screening criteria for potential drug-induced liver injury.6

Overall, the safety profile observed in patients with PsA treated with ixekizumab Q4W is consistent with the safety profile in patients with plaque PsO with the exception of the frequencies of influenza and conjunctivitis.1

Axial Spondyloarthritis: Hepatic Safety From COAST Clinical Trials

An integrated analysis of the phase 3 clinical trials demonstrated no clinically meaningful differences in the frequency of hepatic-related TEAEs across treatment groups. The most commonly reported hepatic-related TEAEs were ALT increased and AST increased. No patient met the laboratory screening criteria for potential drug-induced hepatotoxicity.6

Overall, the safety profile observed in patients with AS/r-axSpA treated with ixekizumab Q4W is consistent with the safety profile in patients with plaque PsO. The safety profile in patients with nr-axSpA treated with ixekizumab 80 mg Q4W up to week 16 is consistent with the previous experience of ixekizumab in other indications.1

Clinical Trials Brief Descriptions

Psoriasis

  • UNCOVER-1, -2, and -3 (N=3866) phase 3 trials in moderate-to-severe plaque psoriasis were integrated to evaluate the safety of ixekizumab in comparison to placebo up to 12 weeks after treatment initiation.

  • The phase 3 trials examined the efficacy and safety of ixekizumab compared with placebo and etanercept (UNCOVER-2 and -3) during induction treatment and vs placebo in maintenance (UNCOVER-1 and -2).7

Psoriatic Arthritis

  • SPIRIT-P1 (N=417) is a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm in patients with active PsA who are naïve to bDMARDs with an extension period of up to 3 years.8

  • SPIRIT-P2 (N=363) is a phase 3, 24-week double-blind, placebo-controlled trial in patients with active PsA and an inadequate response or intolerance to TNF inhibitor, with an extension period of up to 3 years.2

  • SPIRIT-P3 (N=570) consists of a 36-week open-label period followed by a randomized double-blind withdrawal period from week 36 to week 104. This trial is being conducted in patients naïve to bDMARDs.9

Axial Spondyloarthritis

  • COAST-V (N=341) is a phase 3, 16-week double-blind, placebo-controlled trial with an active reference arm and a dose double-blind extension period to 52 weeks in patients with active AS/r-axSpA who are naive to bDMARDs.3

  • COAST-W (N=316) is a phase 3, 16-week double-blind, placebo-controlled trial with a dose double-blind extension period to 52 weeks in patients with active AS/r-axSpA and an inadequate response or intolerance to 1 or 2 TNF inhibitors.4

  • COAST-X (N=303) is a phase 3, 52-week double-blind, placebo-controlled trial in patients with nr-axSpA who are naive to bDMARDs.10

Enclosed Prescribing Information

TALTZ® (ixekizumab) injection, for subcutaneous administration, Lilly

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.

2. Nash P, Kirkham B, Okada M, et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomized, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317-2327. http://dx.doi.org/10.1016/S0140-6736(17)31429-0

3. van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 2018;392(10163):2441-2451. http://dx.doi.org/10.1016/s0140-6736(18)31946-9

4. Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 2019;71(4):599-611. http://dx.doi.org/10.1002/art.40753

5. Griffiths CEM, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541-551. http://dx.doi.org/10.1016/S0140-6736(15)60125-8

6. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

7. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375(4):345-356. http://dx.doi.org/10.1056/NEJMoa1512711

8. Mease PJ, van der Heijde D, Ritchlin CT, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. http://dx.doi.org/10.1136/annrheumdis-2016-209709

9. A long-term efficacy and safety study of ixekizumab (LY2439821) in participants with active psoriatic arthritis (SPIRIT P3). ClinicalTrials.gov identifier: NCT02584855. Updated November 6, 2018. Accessed March 13, 2019. https://www.clinicaltrials.gov/ct2/show/NCT02584855?term=SPIRIT-P3&rank=1.

10. Deodhar A, van der Heijde D, Gensler LS, et al. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64. http://dx.doi.org/10.1016/S0140-6736(19)32971-X

Glossary

AE = adverse event

ALT = alanine aminotransferase

AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis

axSpA = axial spondyloarthritis

AST = aspartate aminotransferase

bDMARD = biologic disease-modifying antirheumatic drug

IgG = immunoglobulin G

nr-axSpA = nonradiographic axial spondyloarthritis

PK = pharmacokinetics

PsA = psoriatic arthritis

PsO = psoriasis

Q4W = every 4 weeks

TEAE = treatment-emergent adverse event

TNF = tumor necrosis factor

ULN = upper limit of normal

Date of Last Review: June 19, 2019


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